Exosomal piRNA profiling revealed unique circulating piRNA signatures of cholangiocarcinoma and gallbladder carcinoma

Abstract

Cholangiocarcinoma (CCA) and gallbladder carcinoma (GBC) are biliary tract cancers with poor five-year survival and high recurrence rates. Both CCA and GBC patients suffer from lack of circulating diagnostic biomarkers at the early stage. Extracellular vesicles, especially exosomes, have been emerged as promising diagnostic sources for cancers due to easy and quick accessibility. Hence, identification of exosomal biomarkers provides a novel strategy for CCA and GBC diagnosis. Here, five CCA patients and four GBC patients were enrolled for exosomal small RNA sequencing. Our data showed that exosomal piwi-interacting RNA (piRNA) populations were altered in the plasma of CCA and GBC patients. In comparison to healthy individuals, 694 and 323 piRNAs were upregulated in CCA and GBC, respectively, while 36 and 191 piRNAs were downregulated. Interestingly, sequencing results predicted that piR-2660989, piR-10506469, piR-20548188, piR-10822895, piR-hsa-23209, and piR-18044111 were upregulated in both CCA and GBC plasma. Importantly, we further included blood samples from 50 health individuals, 40 CCA patients, and 25 GBC patients and found that piR-10506469 were significantly increased in the exosomes of plasma from both CCA and GBC patients. Moreover, we analyzed the expression levels of differentially expressed exosomal piRNAs in the plasma of CCA and GBC patient before and after surgeries and found that piR-10506469 and piR-20548188 were significantly decreased in patients underwent surgeries. Taken together, our data revealed that exosomal piRNAs those are differentially expressed in CCA and GBC plasma may serve as potential biomarkers for the diagnosis of CCA and GBC.

Extracellular vesicles as biomarkers in liver diseases: A clinician's point of view

“…202 Two other preclinical studies found differentially expressed extracellular vesicle RNAs between patients with cholangiocarcinoma and healthy controls. 203,204 To conclude, several subpopulations of extracellular vesicles have the potential to become very useful tools to differentiate cholangiocarcinoma from primary sclerosing cholangitis and other tumours. The use of demanding techniques to measure extracellular vesicles would likely not be a limitation in this setting since these situations are not common and patients are usually referred to expert centres.…”

Circulating exosomal small RNAs are promising non‐invasive diagnostic biomarkers for gastric cancer

“…37 In addition, piR-10506469 were found to be significantly increased in the exosomes of plasma from both cholangiocarcinoma and gallbladder carcinoma patients, indicating it may be serve as the potential cancer biomarker. 38 Exosomes secreted from tumour cells may contain several piRNAs originated from cells, 39 which may be aberrantly expressed in tumour cells. Whether serum exosomal piRNAs are biomarkers for other cancers deserves further study.…”

The Malignant Role of Exosomes as Nanocarriers of Rare RNA Species

“…Importantly, piR-10506469 was further validated in blood samples from a large cohort of patients with GBC and CCA as being significantly increased compared to healthy controls. The same analysis of patients that underwent resection therapy showed that this specific piRNA decreases after tumor removal, together with piR-20548188 [55].…”